The long-term objective of this research program is to seek new information regarding the structure and function of the various proteins involved in blood coagulation, fibrinolysis, and platelet adhesion in order to understand their mechanism of action, their inhibition, their biosynthesis, and their gene structure. In the present grant application, a major focus will be placed on an investigation of the normal and abnormal genes coding for factor XI and the expression of this protein, the isolation and characterization of a human placental coagulant protein that may play an important role in the initiation of blood coagulation, the structure and function of platelet glycoprotein IV, the structure and function of several placental anticoagulant proteins, the structure and function of the a and b subunits of factor XIII and their genes, the gene organization for plasminogen, the structure and function of factor X and the structure of several domains present in plasma protein. The various protein, described above play an important role in the formation of the platelet plug and fibrin generation following vascular damage. One of these proteins (plasminogen) also plays a key role in dissolving the fibrin clot as vascular repair occurs. These proteins are isolated by conventional methods and their amino acid sequence established by amino acid sequence analysis and CDNA cloning. The structure and organization of the normal and abnormal genes coding for these proteins are established by gene cloning and the polymerase chain reaction. The expression of these proteins will be studied in mammalian cell culture after transfection of their cDNAs present in appropriate expression vectors. Various portions of these molecules will also be examined by site-I specific mutagenesis experiments to provide information regarding the role of specific amino acids-and domains in these proteins. It is hoped that this new information will assist in the clinical management of individuals who have vascular damage or injury or suffer from abnormal blood coagulation (such as hemophilia) or abnormal fibrin clot formation leading to coronary thrombosis.